Given that: (1) cancer suppressor p53 is mutated in more than 50% of human cancers of different tissue origin; (2) p53 pathway is altered in about 80% of tumors.; (3) our understanding is incomplete in terms of molecular targets and the oncogenic/malignant pathways involved in mutant p53-overexpressing tumors; (4) cancer causes the highest economic loss compared to all the known causes of death worldwide; and (5) cancer causes the considerable economic loss worldwide, there is an urgent need to find: (i) a cheaper alternative to the existing expensive drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and stall metastatic progression and relapse of mutant p53-overexpressing human cancers.

From therapeutic strategy to Research Findings:

(i) Therapeutic strategy:

This study suggests a therapeutic strategy for stalling the progression of p53-deficient/deleted or mutant-p53 expressing metastatic cancers. By activating tumor suppressor p53’s unmutated “homologous protein such as TAp73/p63” in p53-deficient or mutant-p53 expressing metastatic cancer cells, one can stall their progression.

(ii) Research findings:

A number of studies suggests that the valsartan functions as an anticancer agent. However, the mechanism of action is far from clear.

This study suggests, for the first time, that valsartan, by decreasing the expression of its target gene, it may increase the expression oftumor suppressors genes, such as PTEN, PDCD4, INK4a, BTG2, TAp73α, TIMP3, CCM3/KRIT1 and others. Thereby, it may inhibit the migration and invasion of metastatic cancer cells expressing mutant-p53 (figure1).

Figure 1. Mechanistic insight into how valsartan functions as an anticancer/antimetastatic agent in mutant p53-expressing tumors. Valsartan, by activating tumor suppressor genes, such as PTEN, PDCD4, INK4a, BTG2, TAp73α, TIMP3, CCM3/KRIT1 and others, in metastatic tumors, it may inhibit the progression of mutant-p53 expressing human cancers.

Therapeutic opportunity:

Given the ability ofvalsartanto induce the expression of a number of tumor suppressor genes, pharmacological formulations encompassing “valsartanor its analogues, either alone or in combination with other anticancer drugs,“ may be used to inhibit the progression of p53-mutated invasive metastatic tumors.

Taken together, this study suggests that oncologists may consider treating terminally ill metastatic cancer patients with valsartan, as it may stall the progression of advanced metastatic cancers.